This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hein, S. Articles by Schaper, J. Search for Related Content PubMed PubMed Citation Articles by Hein, S. Articles by Schaper, J. Related Collections Structure Contractile function Physiological and pathological control of gene expression

(Circulation. 2002;106:1302.)
© 2002 American Heart Association, Inc.

Editorial

Giant Molecule Titin and Myocardial Stiffness

Stefan Hein, MD; William H. Gaasch, MD; Jutta Schaper, MD

From the Department of Thoracic and Cardiaovascular Surgery, Kerckhoff-Clinic, Bad Nauheim, Germany (S.H.); the Department of Cardiovascular Medicine, Lahey Clinic, Burlington, Mass (W.H.G.); and the Department of Experimental Cardiology, Max-Planck-Institute, Bad Nauheim, Germany (J.S.).

Correspondence to Jutta Schaper, MD, Max-Planck-Institute, Department of Experimental Cardiology, Benekestr 2, D-61231 Bad Nauheim, Germany. E-mail j.schaper@kerckhoff.mpg.de

Key Words: Editorials • proteins • myocardium

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The beauty of the new titin hypothesis is that the heart is able to change its resting length-tension relationship under chronic stress conditions by isoform switching, thereby rehabilitating the old clinical paradigm of "diastolic tone." The path from hypothesis to reality is rocky, however, as the articles by Wu and Neagoe in this issue of Circulation show.^1,2

See pp 1333 and 1384

Wu et al¹ found that the titin isoforms N2BA/N2B ratio was decreased from a normal ratio of 1.0 to 0.8 in the paced dog heart. Because N2B represents the isoform with stiffer elastic properties, this resulted in an increased passive stiffness in isolated muscle strips. The authors suggest that this "titin-based" stiffness is acting in concert with "collagen-based" stiffness and that it may counteract ventricular dilatation in canine hearts failing because of chronic pacing.

The results are somewhat in contrast with an earlier study by the same group in which a switch to the more extensible isoform N2BA was shown to occur in the subendocardium of canine hearts after 2 weeks of pacing. This seemingly contradictory result might reflect a different time course of titin isoform expression.³

Neagoe et al² report a titin isoform shift from 30:70 (ratio 0.42) of N2BA/N2B in normal human myocardium to 47:53 (ratio 0.89) in nonischemic regions from human hearts transplanted because of coronary artery disease (CAD). Total passive tension was reduced in CAD compared with control, indicating a more compliant behavior of the myocardium. The authors, referring to the well-known increase in . . . [Full Text of this Article]

This article has been cited by other articles:

				O. L. Nelson, C. T. Robbins, Y. Wu, and H. Granzier Titin isoform switching is a major cardiac adaptive response in hibernating grizzly bears Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H366 - H371. [Abstract] [Full Text] [PDF]

				K. A. Clark, J. M. Bland, and M. C. Beckerle The Drosophila muscle LIM protein, Mlp84B, cooperates with D-titin to maintain muscle structural integrity J. Cell Sci., June 15, 2007; 120(12): 2066 - 2077. [Abstract] [Full Text] [PDF]

				S. Reddy, J. C. Osorio, A. M. Duque, B. D. Kaufman, A. B. Phillips, J. M. Chen, J. Quaegebeur, R. S. Mosca, and S. Mital Failure of Right Ventricular Adaptation in Children With Tetralogy of Fallot Circulation, July 4, 2006; 114(1_suppl): I-37 - I-42. [Abstract] [Full Text] [PDF]

				A. B. Borisov, A. Kontrogianni-Konstantopoulos, R. J. Bloch, M. V. Westfall, and M. W. Russell Dynamics of Obscurin Localization During Differentiation and Remodeling of Cardiac Myocytes: Obscurin as an Integrator of Myofibrillar Structure J. Histochem. Cytochem., September 1, 2004; 52(9): 1117 - 1127. [Abstract] [Full Text] [PDF]

				S. F. Nagueh, G. Shah, Y. Wu, G. Torre-Amione, N. M.P. King, S. Lahmers, C. C. Witt, K. Becker, S. Labeit, and H. L. Granzier Altered Titin Expression, Myocardial Stiffness, and Left Ventricular Function in Patients With Dilated Cardiomyopathy Circulation, July 13, 2004; 110(2): 155 - 162. [Abstract] [Full Text] [PDF]

				W. A. Linke, S. Hein, W. H. Gaasch, and J. Schaper Titin Stiffness in Heart Disease * Response Circulation, March 25, 2003; 107 (11): e73 - e73. [Full Text] [PDF]